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Purpose: The purpose of the study was to report on the prognostic value of (99m)Tc-hydrazinonicotinamide (HYNIC) Annexin-V single-photon emission computed tomography (SPECT) imaging in patients suffering from primary squamous cell carcinoma of the head and neck., Methods: Twenty-nine patients diagnosed with a primary untreated head and neck squamous cell carcinoma were included in this study. In all patients, (99m)Tc-HYNIC Annexin-V scintigraphy SPECT was performed before treatment instigation. Tumour-to-background ratios (T/N) of the primary tumour, derived from reconstructed images, as well as clinical variables were obtained in all patients and related to patient outcome. Median follow-up was 22.6 months (range 4.1-55.8 months)., Results: On univariate as well as multivariate analysis, only the (99m)Tc-HYNIC Annexin-V T/N ratio dichotomized using the group median as cutoff value (T/N ratio of 2) was predictive of recurrence-free survival (respectively, p = 0.0000 and 0.000). On univariate analysis, only lymph node status dichotomized according to N0 vs N1-N2-N3 disease and the (99m)Tc-HYNIC Annexin-V T/N ratio dichotomized using the group median as cutoff value (T/N ratio of 2) were predictive of overall survival (p = 0.0051 and 0.0000). When both factors were included in the multivariate model, both N status and the (99m)Tc-HYNIC Annexin-V T/N ratio showed an independent association with overall survival (p = 0.001 for lymph node status and 0.000 for dichotomized (99m)Tc-HYNIC Annexin-V T/N ratio)., Conclusion: (99m)Tc-HYNIC Annexin-V T/N ratios derived from SPECT provides independent prognostic information on disease-free survival and overall survival.

Aim: The aim of this study was to report on the relationship between preradiotherapy and prechemotherapy 99mTc-HYNIC Annexin-V tumor uptake values, reflecting ongoing apoptosis, and outcome to radiotherapy and/or chemotherapy., Methods: Twenty-three cancer patients underwent staging examinations and a 99mTc-HYNIC Annexin-V scintigraphy and subsequent radiotherapy and/or chemotherapy. Tumor-to-background ratios derived from tomographic 99mTc-HYNIC Annexin-V images were related to treatment outcome as assessed by RECIST criteria., Results: Six patients underwent radiotherapy or radiochemotherapy: 4 exhibited response to treatment, 1 had stable, and 1 progressive disease. Corresponding tumor-to-background ratio's were respectively >or=2.3 (in responders), 1.2 in the patient presenting with stable disease and 1 in the patient presenting with progressive disease. Seventeen patients were treated by chemotherapy alone: 8 were progressive, 1 patient presented with stable disease and 8 responded to treatment. In 1/8 progressive patients a tumor-to-background ratio of 1.4 was found, the others showed no uptake. In the patient presenting with stable disease a ratio of 0.1 was found. In the 8 responders, 7 patients had a tumor-to-background ratio >or=1.3 whereas in 1 patient a ratio of 0.3 was found. Tumor-to-background ratios in responders (complete plus partial) (median 2.5, range: 0.3-4.2) were significantly higher when compared to those obtained in non-responders (stable plus progressive disease) (median 1, range: 0.1-1.4) (P<0.001)., Conclusion: The findings presented suggest that 99mTc-HYNIC Annexin-V pretreatment uptake may be useful to predict response to chemo- and radiotherapy.

This study reports on the relationship between quantitative (99m)Tc-HYNIC radiolabelled annexin V tumour uptake measurements, Fas ligand (FasL) expression, matrix metalloproteinase-9 (MMP-9) expression, microvessel density (MVD) and the number of tumour-infiltrating lymphocytes in squamous cell carcinoma of the head and neck (SCCHN) patients. Twenty-eight patients (24 men and 4 women; mean age 59 years, range 43-83 years) suffering from a primary ( n, number of patients=22) or locally recurrent ( n=6) SCCHN were studied. All patients underwent a spiral CT scan, allowing estimation of lesion size in three dimensions, and (99m)Tc-HYNIC annexin V scintigraphy within 1 week of each other. Biopsies or resection of the suspected primary tumour or local recurrence for histopathological analysis were performed on all patients within a period of 10 days following (99m)Tc-HYNIC annexin V scintigraphy. The percentage uptake of the injected dose of (99m)Tc-HYNIC annexin V in visible tumour lesions on scintigrams divided by the tumour volume, derived from CT, was related to MVD and to histological score (HSCORE) values for MMP-9 and FasL expression as well as to the number of tumour-infiltrating lymphocytes (CD45 staining). Median percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images was 0.0001% (SD 0.0001%) at 5-6 h p.i. (range: 0.000007-0.0003%). Mean HSCORE for MMP-9 tumour staining was 2.1 (SD 0.84). Mean HSCORE for FasL tumour staining was 2.49 (SD 0.92). At the sites of tumour containing the highest number of vessels, the mean MVD was 20 vessels/field at the hot spot (range 1-73). The median number of tumour-infiltrating lymphocytes was 500 (range 100-5,000). The percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images correlated linearly with FasL HSCORES( r=0.47, P=0.02). No correlation was found between the percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images and MMP-9 HSCORES, MVD or the number of tumour-infiltrating lymphocytes. MVD correlated significantly with MMP-9 HSCORES ( r=0.44, P=0.03).

Because of its potential to allow for noninvasive, repetitive, and selective in vivo identification of the site and extent of apoptotic cell death and for monitoring cell death kinetics without the need for invasive biopsy, radiolabeled annexin-V is of major clinical relevance. This paper reviews available preclinical and clinical data on radiolabeled annexin-V pertaining to the domain of monitoring response to radiotherapy and chemotherapy, focusing especially on advantages and drawbacks of the different labeling procedures for the radiolabeling of annexin-V.

In this study, the potential of 99mTc-HYNIC Annexin-V scintigraphy to visualize primary head and neck carcinoma was assessed and compared with computed tomography (CT) findings and histology. Eighteen patients suspected of having primary head and neck carcinoma underwent a spiral CT scan and 99mTc-HYNIC Annexin-V scintigraphy within 1 week of each other, followed by resection of the suspected lesion. Results obtained by CT and scintigraphy were compared vs. histopathology. The diagnosis was primary head and neck carcinoma in 18 patients, accompanied by lymph node involvement in seven patients. 99mTc-HYNIC Annexin-V uptake was identified in five patients on planar images and in 17 patients on tomographic images (single-photon emission computed tomography, SPECT), corresponding to the pathological regions identified by CT. In the remaining patient, CT and 99mTc-HYNIC Annexin-V scintigraphy were false negative. In 11 patients, SPECT and CT scan were concordant, identifying all primary lesions and two sites of lymph node involvement. In the six remaining patients, CT and SPECT accurately identified the primary lesion, but were discordant with regard to the existence of lymph node involvement. In five of six patients, SPECT failed to identify lymph node involvement, whereas CT scan did not. In the remaining patient, CT scan was false positive for lymph node involvement, whereas SPECT was not. In this series, 99mTc-HYNIC Annexin-V allowed for the visualization of all primary head and neck tumours identified by CT scan, but failed to identify most of the sites of lymph node involvement.

Purpose: Radiolabeled annexin V may allow for repetitive and selective in vivo identification of apoptotic cell death without the need for invasive biopsy. This study reports on the relationship between quantitative technetium-99m- (99mTc-) 6-hydrazinonicotinic (HYNIC) radiolabeled annexin V tumor uptake, and the number of tumor apoptotic cells derived from histologic analysis., Patients and Methods: Twenty patients (18 men, two women) suspected of primary (n = 19) or recurrent (n = 1) head and neck carcinoma were included. All patients underwent a spiral computed tomography (CT) scan, 99mTc-HYNIC annexin V tomography, and subsequent surgical resection of the suspected primary or recurrent tumor. Quantitative 99mTc-HYNIC annexin V uptake in tumor lesions divided by the tumor volume, derived from CT, was related to the number of apoptotic cells per tumor high-power field derived from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assays performed on sectioned tumor slices., Results: Diagnosis was primary head and neck tumor in 18 patients, lymph node involvement of a cancer of unknown primary origin in one patient, and the absence of recurrence in one patient. Mean percentage absolute tumor uptake of the injected dose per cubic centimeter tumor volume derived from tomographic images was 0.0003% (standard deviation [SD], 0.0004%) at 1 hour postinjection (PI) and 0.0001% (SD, 0.0000%) at 5 to 6 hours PI (P =.012). Quantitative 99mTc-HYNIC annexin V tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered., Conclusion: In the absence of necrosis, absolute 99mTc-HYNIC annexin V tumor uptake values correlate well with the number of apoptotic cells derived from TUNEL assays.